The Systolic Blood Pressure Intervention Trial (SPRINT) is a 2-arm, multicenter, randomized clinical trial designed to test whether a treatment program aimed at reducing systolic blood pressure (SBP) to a lower goal than currently recommended will reduce cardiovascular disease (CVD) risk. About 9250 participants with SBP greater than or equal to 130 mm Hg and at least one additional CVD risk factor will be recruited at approximately 80 clinics within 5 clinical center networks (CCNs) over a 2-year period, and will be followed for 4-6 years. Approximately 4300 participants will have chronic kidney disease (CKD), and about 3250 will be aged 75 or older. The primary outcome is the first occurrence of a myocardial infarction (MI), acute coronary syndrome (ACS), stroke, heart failure (HF), or CVD death. Secondary outcomes include all-cause mortality, decline in renal function or development of end stage renal disease (ESRD), dementia, decline in cognitive function, and small vessel cerebral ischemic disease.